PB2171: POTENTIAL ROLE OF FACTOR XII POLYMORPHISM IN PATIENTS WITH MYELOPROLIFERATIVE NEOPLASMS
Authors: Elizaveta Efremova, Sergey Kapustin, Nadezhda Nemscveridze, Anna Pirkhalo, Ekaterina Mileeva, Natalia Silina, Natalia Korsakova, Olesia Matvienko, Ludmila Papayan, Sergey Voloshin
Journal: HemaSphere (2023)

Topic: 15. Myeloproliferative neoplasms - Biology & Translational Research Background: The most common forms of Ph-negative myeloproliferative neoplasmas (MPN) are polycythemia vera (PV), essential thrombocythemia (ET) and primary myelofibrosis (PMF). These conditions are characterized by increased cytokines production, extramedullary hematopoiesis and replacement of bone marrow with fibrotic tissue. Factor XII (FXII) is a zymogen that plays important role in hemostasis, activation of growth factors in tissues, immune-mediated inflammation and fibrosis in different organs. FXII stimulates Akt2 to initiate neutrophil adhesion, migration, and chemotaxis - priming events leading to NETosis (neutrophil extracellular traps) which is associated with high frequency of thrombosis in MPN patients. The level and activity of FXII in blood plasma is associated with FXII 46 C/T gene polymorphism. Aims: To assess frequency and clinical significance of FXII 46 C/T gene polymorphism in patients with MPN. Methods: We analyzed 88 patients (34 men and 54 women) with MPN, of them 33 PV, 25 ET, 20 PMF and 10 with secondary (postPV/ET) myelofibrosis (SMF). Median age of the group was 57 years (range 29 – 80). All individuals originated from the North-Western region of Russia and gave informed consent for participation in the study. FXII 46 C/T gene polymorphism was discriminated by PCR-RFLP technique. The differences in genotype distributions between groups were estimated by Fisher`s exact test. Odds ratios (OR), their 95% confidence intervals (CI) and p-values were calculated by using the GraphPad Prism software. Results: Homozygousity for the FXII 46T allele was found in 2 patients (6%) with PV, 1 patient (4%) with ET, 4 patients (20%) with PMF and 3 (30%) patients with SMF. Thus, the FXII 46TT genotype was more prevalent in the group of MPN patients with the signs of fibrosis (23.3% vs. 5.2% in other patients, OR=5.6, 95%CI: 1.3-23.5, p=0.028). Nine out of ten patients with secondary MF were treated with hydroxyurea including period before transformation. One patient with postET fibrosis was treated with anagrelide. The median time of treatment was 34 months (range 2-64). The rate of thrombosis was comparable between the groups of MPN patients with or without 46TT genotype (30.0% and 34.6%, respectively, p = 0,73). Factor XII activity was studied only in patients with increased aPTT, and comprehensive data for analysis are not available. These results are intermediate. Clinical significance of the FXII 46 C/T gene polymorphism to myelofibrosis in MPN patients should be evaluated in further studies. Summary/Conclusion: We suggest that genetic variability of FXII can contribute to fibrosis risk in bone marrow of PV and ET patients. Relationship of FXII 46 C/T gene polymorphism with level and activity of FXII in plasma and bone marrow will be evaluated. Keywords: Myeloproliferative disorder, Coagulation factors, Myelofibrosis